UWorld 3/19

Other markers of osteoblast activity include

N-terminal propeptide of type 1 procollagen (PINP), which is released during post-translation cleavage of type 1 procollagen before its assembly into mature type 1 collagen fibrils.

E. Ringed sideroblasts (10%)

Ringed sideroblasts are abnormal erythrocyte precursors found in myelodysplastic syndrome (MDS) and characterized by mitochondrial iron accumulation surrounding the nucleus. Patients with MDS typically have petechiae, weakness, and recurrent infections; splenomegaly is uncommon.

Prostate adenocarcinoma is a glandular tumor that often spreads to the bones; however, it generates_____bone lesions, not radiolucent bone lesions. Prostate cancer does not generally impinge on the urethra (no urinary symptoms) and is usually associated with a nodule on prostate examination. This patient's intermittent difficulty urinating and diffusely enlarged prostate with no nodules likely indicate benign prostatic hyperplasia.

sclerotic (osteoblastic)

Which of the following findings is most likely to be seen in this patient? A. Intraerythrocytic ring forms (6%)

seen in malaria

Although lymphadenopathy usually occurs secondary to the proliferation of inflammatory cells in response to infection, it is less commonly due to a clonal expansion of malignant cells. Malignancy should be suspected when lymph node enlargement is associated with any of the following features: Generalized or _____ location Firm, immobile, nontender quality >2 cm or increasing size Systemic features (eg, weight loss, night sweats)

supraclavicular The supraclavicular nodes drain the chest (ie, pulmonary system, mediastinum) and abdomen (ie, gastrointestinal and genitourinary tracts). Therefore, enlargement of these lymph nodes is unlikely to be caused by common childhood infections and always warrants further workup (eg, complete blood count, ultrasound) for an associated malignancy

HPV infects basal epithelial cells through small breaks in the skin or mucosal surfaces. It has a predilection for stratified squamous epithelium, which is found in the anal canal, vagina, and cervix. In the respiratory tract, the _____ are the only area covered with stratified squamous epithelium. The vocal cords undergo near-constant friction and abrasion to produce speech. Stratified squamous epithelium is protective, as deeper cells can replace surface cells that are damaged.

true vocal cords

NF-kB signaling promotes transcription of proinflammatory cytokines (eg, ______), leading to local inflammation, immune cell recruitment, and systemic effects (eg, fever, malaise, lethargy, poor feeding). It also stimulates antigen-presenting cells to increase phagocytosis, antigen display, and expression of costimulatory molecules (eg, CD80/86) for T- and B-cell activation, thereby triggering a strong adaptive immune response.

tumor necrosis factor-alpha, IL-1, IL-6, IL-12

Porphyria Cutanea Tarda is caused by ______ deficiency, which is either inherited or (more commonly) acquired, manifesting in the presence of iron and of susceptibility factors (eg, alcohol [as in this patient], smoking, halogenated hydrocarbons, hepatitis C, HIV). Photosensitivity presents as vesicle and blister formation on sun-exposed areas as well as edema, pruritus, pain, and erythema. Deficiencies in coproporphyrinogen oxidase, protoporphyrinogen oxidase, or ferrochelatase can also result in photosensitivity.

uroporphyrinogen decarboxylase (UROD)

The Fc receptor (CD____) on phagocytic cells binds to opsonized (eg, IgG-bound) foreign pathogens, leading to phagocytic destruction. The Fc receptor on natural killer cells mediates their ability to destroy infected or cancerous cells by antibody-dependent cellular cytotoxicity

16

______ is an autosomal recessive condition caused by mutations in the genes responsible for the repair of interstrand DNA crosslinks. It is the most common inherited cause of aplastic anemia and presents with short stature, absent thumbs, and increased malignancy risk.

Fanconi anemia

C. Myeloid cells with azurophilic rodlike granules (25%)

Myeloid cells with azurophilic rodlike granules (Auer rods) can be found in acute myeloid leukemias, which do not typically cause hepatosplenomegaly.

______ helps leukocytes migrate from the bloodstream to tissue by binding to intercellular adhesion molecule-1 on the extracellular matrix of the endothelium. It also helps macrophages, neutrophils, and natural killer cells generate complement receptors, which recognize and phagocytose foreign peptides.

Beta-2 integrin (CD18)

A 32-year-old man is started on infliximab for treatment of refractory Crohn disease. Ten days later, he develops joint pain and a pruritic skin rash. Skin biopsy shows scattered areas of fibrinoid necrosis and neutrophil infiltration involving his small blood vessels. Which of the following findings is most likely to accompany this patient's condition? A. Candida antigen anergy (%) B. Decreased serum C3 level (%) C. Increased serum IgE level (%) D. Low serum IgA level (%) E. Neutrophilia (%) F. Severe thrombocytopenia (%)

B. Decreased serum C3 level (%) This patient's symptoms and biopsy findings are suggestive of acute serum sickness, a condition caused by tissue deposition of circulating immune complexes (type III hypersensitivity). The most common manifestations include fever, pruritic skin rash, and arthralgias that begin 7-14 days after exposure to an antigen. Lymphadenopathy and proteinuria may also occur in some patients. Histologic examination of affected tissues typically shows small vessel vasculitis with fibrinoid necrosis and intense neutrophil infiltration. Deposition of IgG and/or IgM complement-fixing antibodies results in localized complement consumption and hypocomplementemia (decreased serum C3 levels). Serum sickness can occur following administration of antigenic heterologous proteins such as chimeric monoclonal antibodies (eg, rituximab and infliximab) or nonhuman immunoglobulins (eg, venom antitoxins). A serum sickness-like reaction is also associated with the use of certain nonprotein drugs (eg, penicillin, cefaclor, and trimethoprim-sulfamethoxazole)

35-year-old woman comes to the hospital due to sudden-onset numbness in her left arm and face. The patient has had generalized headache, dyspnea on exertion, and easy fatigability for several days but no weakness. She has a history of well-controlled asthma. Temperature is 37.7 C (99.9 F), blood pressure is 110/60 mm Hg, and pulse is 80/min. Light touch sensation is decreased in the left upper extremity and the lower left side of the face. Strength and reflexes are normal. Cardiopulmonary and abdominal examinations are unremarkable. There is no skin rash. Laboratory results are as follows: Hemoglobin 8.6 g/dL Platelets 24,000/mm3 Blood urea nitrogen 32 mg/dL Creatinine 1.9 mg/dL PT and PTT are normal. Peripheral blood smear shows numerous schistocytes. Urinalysis is positive for mild proteinuria. Which of the following is the most likely underlying cause of this patient's current condition? A. IgA immune complex deposition (%) B. Impaired cleavage of von Willebrand factor (%) C. Plasma cell proliferation (%) D. Rupture of atheromatous plaque (%) E. Systemic coagulation factor activation (%)

B. Impaired cleavage of von Willebrand factor (%)

Class I HLA proteins (eg, HLA ___) are expressed by all nucleated cells and present endogenous antigens to CD8+ cytotoxic T cells.

B27

how to measure oxygen content of the arterial blood

I think this is just saying that the oxygen content of arterial blood is equal to oxygen bound to hemoglobin + oxygen dissolved in the blood

A 25-year-old woman comes to the office for an initial evaluation of low mood. Since moving to a new apartment 3 weeks ago, the patient has felt sad and has not been sleeping well. She says, "My landlord won't allow pets in the building. I miss my dog so much. I know my mood would improve if I could get a letter from you saying my dog can live with me." The patient's dog is currently staying with her parents, who live a few miles away from her. Which of the following statements by the physician is the most appropriate? A. "Fortunately, your dog is able to live nearby with your parents; what do you think about spending more time at their house?" (%) B. "Having your dog may help you feel better temporarily; let's discuss options that would allow you to develop long-term coping skills." (%) C. "I can see you miss your dog very much; let's start by talking about the mood symptoms you've been experiencing." (%) D. "It must be difficult not having your dog around; what made you decide to move into an apartment that does not allow pets?" (%) E. "Not having your dog live with you seems to be causing a lot of distress; I can write a letter for your dog." (%)

C. "I can see you miss your dog very much; let's start by talking about the mood symptoms you've been experiencing." (%) In this initial patient encounter, the physician is faced with a specific request for an emotional support animal letter but has very limited information. Although physicians should be responsive to a patient's concerns, they should not feel pressured to make a recommendation before fully evaluating the patient. The best approach is to validate the patient's concerns and gather more information on which to base a decision

A newborn girl is admitted to the neonatal intensive care unit with jaundice, hepatomegaly, and generalized edema. She was born by vaginal delivery to a 32-year-old woman, gravida 2, para 2, who received minimal prenatal care. The infant's laboratory results show a hemoglobin level of 6 g/dL and a positive direct Coombs test. A peripheral blood smear shows many nucleated erythrocytes. The infant has significant respiratory distress due to pleural effusions and ascites and dies soon after birth. Autopsy shows areas of extramedullary hematopoiesis in many tissues. Which of the following is the most likely cause of this patient's condition? A. Abnormal hemoglobin polymerization (2%) B. Absence of alpha globin chains (7%) C. Erythrocyte opsonization by maternal antibodies (76%) D. Glucose-6-phosphate dehydrogenase deficiency (2%) E. Red blood cell lysis by fetal antibodies (11%)

C. Erythrocyte opsonization by maternal antibodies (76%) Hemolytic disease of the newborn (erythroblastosis fetalis) results from the destruction of fetal red blood cells by maternal antibodies directed against fetal erythrocyte antigens. These antibodies are IgG antibodies, the only class of antibody able to cross the placenta. Erythroblastosis fetalis is most commonly caused by Rhesus (Rh) incompatibility (particularly the D antigen). Rh sensitization can occur in an Rh(D)− mother during pregnancy with an Rh(D)+ fetus due to small amounts of fetal blood crossing the placenta and entering the maternal circulation. These erythrocytes are viewed as foreign by the maternal immune system and induce the production of anti-Rh(D) IgG antibodies. In subsequent pregnancies with an Rh(D)+ fetus, these antibodies cross the placenta and opsonize fetal erythrocytes, causing hemolysis. This results in a positive direct Coombs test (indicating autoimmune hemolysis), profound anemia, jaundice (possibly leading to kernicterus), and generalized edema (hydrops fetalis due to accumulation of interstitial fluid). The severe anemia also stimulates release of immature, nucleated erythrocytes and leads to persistent extramedullary hematopoiesis in the liver, spleen, and other tissues (hepatosplenomegaly)

24-year-old pregnant woman comes to the emergency department in active labor at full term. The patient has a history of HIV from injection drug use. She is not adherent with antiretroviral therapy and has had no recent testing of CD4 count or plasma viral load. Physical examination shows regular uterine contractions, ruptured amniotic membranes, and a fully dilated cervix. A decision is made to continue with the vaginal delivery due to advanced labor. Intravenous zidovudine is administered to the patient during the delivery and to the infant immediately after birth. This medication helps decrease the risk of perinatal transmission by inhibiting which of the following components of viral genome replication? A. Folate-dependent uracil methylation (%) B. Integration of viral DNA into the host genome (%) C. Nucleoside phosphorylation (%) D. Phosphodiester bond formation (%) E. Proper base pairing and hydrogen bond formation (%)

D. Phosphodiester bond formation (%)

64-year-old man comes to the office due to 3 months of constant, dull, low back pain that is worse with movement. The patient has also had intermittent episodes of difficulty urinating over the last year. He has no other medical conditions and takes no medications. The patient smoked a pack of cigarettes daily for 15 years but quit 10 years ago. Vital signs are within normal limits. On physical examination, the lungs are clear and heart sounds are normal. The abdomen is soft and nontender with no hepatosplenomegaly. Digital rectal examination shows a diffusely enlarged prostate with no nodules. Laboratory testing reveals a serum creatinine level of 1.9 mg/dL. Urine dipstick testing is negative, but 24-hour urinary protein excretion is elevated. Urine microscopy shows waxy, laminated casts. Imaging of the spine demonstrates diffuse osteopenia and multiple irregular, radiolucent lesions in the thoracic and lumbar vertebrae. Biopsy from one of the bone lesions is most likely to reveal which of the following histopathological findings? A. Branching papillae lined by cuboidal cells with overlapping nuclei (%) B. Infiltrating glandular cells with substantial adjacent osteoblasts (%) C. Large, malignant cells containing keratin and intercellular bridges (%) D. Clusters of mature plasma cells and plasmablasts (%) E. Sheets of round or polygonal cells with abundant clear cytoplasm (%)

D. Clusters of mature plasma cells and plasmablasts (%)

A 2-year-old boy is brought to the emergency department due to high fever and malaise for the past 4 days. His parents say that he began limping yesterday and now refuses to walk. The patient has had no recent travel or exposure to anyone with similar symptoms. Temperature is 39.4 C (103 F). Passive range of motion of the hips, knees, and ankles does not elicit pain. There are no joint effusions. The patient refuses to bear weight. An intravenous radiotracer that localizes to areas of increased osteoblastic activity is administered, and several images are obtained to find areas with atypical activity. Abnormally increased uptake of the radiotracer is most likely to be seen in which of the following areas? A. Flat bone (%) B. Long bone diaphysis (%) C. Long bone epiphysis (%) D. Long bone metaphysis (%) E. Vertebral body (%)

D. Long bone metaphysis (%) The most common cause of osteomyelitis in children is hematogenous spread of bacteria, which may be introduced by minor (often unnoticed) trauma to a distant site. Infection in children classically occurs in the metaphyses of long bones (eg, femur, tibia) because this region is highly vascular yet contains slow-flowing sinusoids that are conducive to bacterial seeding. Bacterial seeding within the metaphysis initially causes acute inflammation of the bone marrow, with focal hyperperfusion and increased radiotracer uptake within the affected region. Persistent inflammation within the confined bony space leads to increased intramedullary pressure, which compromises blood flow and forces infectious exudate into the cortex and periosteum. Without treatment, the infection can progress to chronic suppurative osteomyelitis, in which necrotic bone (ie, sequestrum) serves as an infectious reservoir and sinus tracts develop to drain away the purulent material

____ is a payment arrangement in which an insurer pays a provider for each individual service provided at a pre-arranged, discounted rate. Employers would not generally negotiate a fee-for-service contract directly with a provider.

Discounted fee-for-service

By contrast, HLA class II proteins (eg, ____ alleles) are expressed by antigen-presenting cells (eg, macrophages, dendritic cells) and present predominantly foreign antigens to CD4+ helper T cells. Conditions associated with HLA class II genotypes include rheumatoid arthritis, type I diabetes mellitus, and celiac disease.

DR, DP, DQ

The H band is the region of the sarcomere containing only thick (myosin) filaments. On electron microscopy, the H band is a portion of the A band that straddles the M line. The A band corresponds to the thick filaments in the sarcomere and includes portions overlapped by thin (actin) filaments (Choice B). During muscle contraction, the thin filaments slide over the thick filaments toward the M line, reducing the length of the H band. The A band always remains the same length.

E is the region of only thick filaments

A 28-year-old man comes to the emergency department due to anxiety, weakness, dyspnea, and headaches. He is a graduate student in chemistry and was accidentally exposed to nitrites in his research laboratory. Physical examination is notable for cyanosis that is not improved by administration of supplemental oxygen via facemask. Analysis of a sample of arterial blood drawn from this patient prior to any oxygen supplementation is most likely to reveal normal values for which of the following? A. Bound fraction of oxygen in the arterial blood (%) B. Oxygen carrying capacity of the arterial blood (%) C. Oxygen content of the arterial blood (%) D. Oxygen delivery to peripheral tissues (%) E. Partial pressure of oxygen in the arterial blood (%)

E. Partial pressure of oxygen in the arterial blood (%) Iron bound to heme is normally in the reduced ferrous (Fe2+) state. Nitrites cause poisoning by inducing the conversion of this heme iron to the oxidized ferric (Fe3+) state, leading to the formation of methemoglobin. With iron in the oxidized ferric state, methemoglobin is unable to bind oxygen. In addition, the affinity of any residual ferrous iron in the hemoglobin tetramer is increased, causing a leftward shift of the oxygen-dissociation curve. However, the partial pressure of oxygen in blood, which represents the amount of oxygen dissolved in the plasma, is unchanged.

A 35-year-old woman, gravida 1, para 0, at 12 weeks gestation comes to the office for evaluation of genital warts. She first noticed the warts last week and is concerned that it has persisted. The patient has occasional mild pruritus but no pain. She is currently sexually active with her boyfriend and engages in oral and vaginal intercourse. Examination shows several verrucous, skin-colored lesions over the labia majora. The patient asks whether the lesion could affect her future child. The virus involved in this patient's condition also has an affinity to infect which of the following structures? A. Alveoli (%) B. False vocal cords (%) C. Paranasal sinuses (%) D. Trachea (%) E. True vocal cords (%)

E. True vocal cords (%)

A 28-year-old man comes to the office due to a 4-month history of pain and stiffness in the lower back and neck. Symptoms are worse with prolonged rest and in the early morning. The patient also has fatigue and poor sleep. He has no other medical conditions and takes no medications. Vital signs are normal. Examination shows limited forward bending of the trunk. Lower extremity muscle power and reflexes are normal. Which of the following is most likely to confirm the diagnosis? A. Complete blood count (%) B. Erythrocyte sedimentation rate (%) > Nerve conduction Studies D. Rheumatoid factor level (%) E. X-ray of the pelvis (%)

E. X-ray of the pelvis (66%)

______ is the drug of choice for the treatment of anaphylactic shock due to its ability to reverse all of the pathophysiologic mechanisms of anaphylaxis. Stimulation of α1 receptors counteracts the vasodilatation of cutaneous and viscera vasculature, thus increasing blood pressure. Epinephrine-mediated increases in cardiac contractility (β1 effect) and cardiac output also increase blood pressure and improve peripheral perfusion. Epinephrine-induced stimulation of β2 receptors results in bronchodilatation, making it also a popular choice for the treatment of severe asthmatic reactions

Epinephrine

______ is an arrangement in which an insurer pays a provider a single payment to cover all the expenses associated with an incident of care. This is most commonly done for elective surgeries, in which the global payment covers the surgery as well as any pre- and post-operative visits needed.

Global payment

B. Lymphocytes with cytoplasmic projections (46%)

Hairy cell leukemia

Difference in DNA Polymerase I and III

I also has the ability to remove RNA primers

LPS is a very long, heat-stable molecule arranged into three regions: O antigen, core polysaccharide, and Lipid A. _____ is toxic to mammalian cells and acts as a virulence factor by inducing the release of endogenous pyrogens (eg, IL-1, prostaglandins) and inflammatory mediators (eg, TNFa, interferon) from activated macrophages. These cytokines cause the manifestations of septic shock: fever, hypotension, increased vascular permeability with third-spacing of fluids, and organ failure

Lipid A

This measures the pressure of oxygen dissolved in the blood and how well oxygen is able to move from the airspace of the lungs into the blood.

Partial pressure of oxygen (PaO2).

Explain phenotypic mixing for viruses

The acquisition of a new viral surface protein is often all that is necessary for a virus to infect a new type of host cell. In this scenario, avian and human influenza virus particles infect host pig cells; certain progeny avian virus particles obtain some of the surface components (eg, sialic acid receptors) of the human influenza virus, allowing the avian virus to infect human cells. This exchange is an example of phenotypic mixing, which generally occurs when a host cell is coinfected with 2 viral strains and progeny virions contain unchanged parental genome from one strain and nucleocapsid (or envelope) proteins from the other strain. However, because there is no change in the underlying viral genomes (no genetic exchange), subsequent progeny will revert to having only avian influenza type surface proteins and will again be noninfectious to human epithelium

A 22-year-old man comes to the office due to recurrent blistering on the back of his hands and forearms for the past several years. The patient usually develops small itchy spots but lately has had large blisters that heal with hyperpigmentation after rupturing. He has used over-the-counter topical hydrocortisone and emollients, but the symptoms have not improved. The patient works as a night security guard and has had no exposure to chemicals or animals. He drinks 2-3 cans of beer daily. Physical examination shows vesicles and erosions on the dorsum of both hands. Which of the following enzymes is most likely deficient in this patient? A. δ-Aminolevulinate dehydratase (%) B. δ-Aminolevulinate synthase (%) C. Bilirubin glucuronyl transferase (%) D. Porphobilinogen deaminase (%) E. Uroporphyrinogen decarboxylase (%)

This patient most likely has porphyria cutanea tarda (PCT), the most common disorder of porphyrin (eg, heme) synthesis. Enzyme deficiencies in the early steps in porphyrin synthesis cause abdominal pain and neuropsychiatric manifestations (due to metabolite buildup) without photosensitivity. Late step (ie, following porphobilinogen [PBG] conversion) derangements (eg, PCT) cause photosensitivity, which is thought to be due to the accumulation of porphyrinogens that react with oxygen on excitation by ultraviolet (sun) light. PCT is caused by uroporphyrinogen decarboxylase (UROD) deficiency, which is either inherited or (more commonly) acquired, manifesting in the presence of iron and of susceptibility factors (eg, alcohol [as in this patient], smoking, halogenated hydrocarbons, hepatitis C, HIV). Photosensitivity presents as vesicle and blister formation on sun-exposed areas as well as edema, pruritus, pain, and erythema. Deficiencies in coproporphyrinogen oxidase, protoporphyrinogen oxidase, or ferrochelatase can also result in photosensitivity.

This patient has septic shock (ie, fluid-refractory hypotension in a patient with sepsis) as a result of the release of bacterial endotoxins into the bloodstream. Endotoxins are found in the outer membrane of Gram-negative bacteria (eg, E. coli), which is composed of ______

lipopolysaccharide (LPS). LPS is released by destruction of the bacterial cell wall or during cell division.

Medical interviewing is best initiated with

an open-ended question. This invites the patient to describe their condition in their own words and gives the physician insight into the patient's major concerns, which can be addressed with more specific questions later in the interview. Examples of open-ended questions include: "What brings you in today?" and "What is that like for you?" In contrast, a closed-ended question requires only a yes/no response and does not encourage conversation/exploration.

Dyspnea, hypotension, and tachycardia soon after administration of β-lactam antibiotics are suggestive of

anaphylactic shock. Hypotension occurs in anaphylactic shock secondary to collapse of peripheral vascular resistance, increases in vascular permeability, and leakage of capillary fluid. Stimulation of the smooth muscle tone within the bronchial wall, along with an increase in bronchial secretion, accounts for the dyspnea seen in anaphylaxis. Skin symptoms (urticaria and angioedema) may occur secondary to vasodilatation and increased vascular permeability of skin capillaries. Increases in GI smooth muscle tone may result in vomiting, abdominal cramps, and diarrhea

The seronegative spondyloarthropathies include

ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthritis associated with inflammatory bowel disease.

This homeless patient has hypoxia, bilateral interstitial infiltrates, and a positive silver stain indicating likely Pneumocystis pneumonia (PCP), an atypical fungal infection caused by the opportunistic pathogen P jirovecii. Inhalation of the organism leads to inoculation of the alveolar space. Healthy individuals rarely develop symptoms as alveolar monocytes and macrophages are stimulated by the cell-mediated immune response to rapidly clear the organism. However, patients with impaired _____, often cannot eliminate the pathogen.

cell-mediated immunity, particularly those with untreated AIDS (CD4 count <200/mm3)

This patient's symptoms and biopsy findings are suggestive of acute serum sickness, a condition caused by tissue deposition of circulating immune complexes (type III hypersensitivity). The most common manifestations include fever, pruritic skin rash, and arthralgias that begin 7-14 days after exposure to an antigen. Lymphadenopathy and proteinuria may also occur in some patients. Histologic examination of affected tissues typically shows small vessel vasculitis with _____ and _____. Deposition of IgG and/or IgM complement-fixing antibodies results in _____ Serum sickness can occur following administration of antigenic heterologous proteins such as chimeric monoclonal antibodies (eg, rituximab and infliximab) or nonhuman immunoglobulins (eg, venom antitoxins). A serum sickness-like reaction is also associated with the use of certain nonprotein drugs (eg, penicillin, cefaclor, and trimethoprim-sulfamethoxazole)

fibrinoid necrosis and intense neutrophil infiltration localized complement consumption and hypocomplementemia (decreased serum C3 levels).

hydroxyurea also shifts globin gene transcription from the beta globin locus to the _____ locus (via unclear mechanisms), thereby increasing circulating levels of fetal hemoglobin (HB F)

gamma globin

Lipid A is toxic to mammalian cells and acts as a virulence factor by inducing the release of endogenous pyrogens (eg, ________ from activated macrophages. These cytokines cause the manifestations of septic shock: fever, hypotension, increased vascular permeability with third-spacing of fluids, and organ failure

pyrogens: IL-1, prostaglandins and inflammatory mediators- TNFa, interferon